Synthesis of aliphatic and alicyclic ethers

ABSTRACT

Aliphatic and alicyclic hydroperoxides may be converted to their corresponding ethers by reacting said hydroperoxides with a suitable alcohol in the presence of an acid and a metal catalyst.

SYNTHESIS OF ALIPHATIC AND ALICYCLIC ETHERS CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation-in-part of U.S. Ser. No. 873,093, tiled Oct. 3l, 1969 and now abandoned, in the name of John O. Turner and entitled IM- PROVED SYNTHESIS OF ALIPHATIC AND ALI- CYCLIC ETHERS.

BACKGROUND OF THE INVENTION This invention reltates to an improved process for the production of aliphatic and alicyclic ethers. More particularly, this invention relates to the increased rate of conversion of aliphatic and alicyclic hydroperoxides to the corresponding ethers by reacting them with a suitable alcohol in the presence of an acid and a metal catalyst.

In copending application, U.S. Ser. No. 873,094, filed Oct. 31, 1969, in thename of John O. Turner, there is described a novel method for converting aliphatic and alicyclic hydroperoxides to the corresponding ethers which comprises contacting said hydroperoxides with a suitable alcohol in the presence of anacid catalyst. This method, while unique and highly effective, nevertheless is characterized in (l) having a reaction time of from about 5 to as much as about 40l hours or more, and generally from about l0 to20fhours; and (2)'requiring an acid concentration of 30 to 60 weight percent based onthe weight of thevacid-alcohol mixture. Thus, an increase in the reaction rate of this process at a lower acid concentration would be highly desirable in that it would permit the use of much'smaller reactors to obtain the same yield, or alternatively increases the yield with time, while at the same time avoiding the use of highly concentrated acids and effecting a cost savings as well.

SUMMARYOF THE :Nvt-:NUON

DESCRIPTION OF THE INVENTION This process is conveniently carried out by simply mixing thedesired hydroperoxide starting material in a suitable alcoholic acid medium for about one-half to 5 hours, and preferably for about 2 to 4 hours', in the presence of a metal salt catalyst, and recovering theresulting ether. y

In order to assure optimum results, it is important that the ratios of the'` hydroperoxide, the acid, the -alcohol and the metal salt be kept within certain specified ranges. Thus, the alcohol should be present in a two-totwelve-fold molar excess, based on the moles'of hydroperoxide, and preferably from about a seven-to-tenfold molar excess of the alcohol.

The amount of acid should, as mentioned above, be based on the amount of alochol presentin order to provide a 5 to 30 weight percent concentration of the lacid based on the total weightof the acid-alcohol mixture.

comprise pure The preferred weight percent of acid is about l5 to 20 percent. ln carrying out this reaction, it has been found to be particularly advantageous, after removing the ether from the reaction mixture, to recycle the acid to the reaction medium after addition of sufficient alcohol to readjust the acid concentration to the desired level, thereby enhancing the yield of ether which is otherwise entrapped with the acid.

The acid employed should be a concentrated acid, as for example, hydrochloric, phosphoric, polyphosphoric, sulfuric, perchloric, various sulfonic acids or the like, as well as acid-treated molecular sieves. Preferably, the `acid is sulfuric acid in concentrations of from about 90 percent to 20 percent oleum.

The alcohol is desirably a lower aliphatic alcohol having from l to 4 carbon atoms. Of these, methanol is preferred. However, depending upon the alkyl moiety desired in forming the resulting ether, other alcohols may be employed instead. Thus, for example, if ethyl t-butyl ether is desired rather than methyl t-butyl ether, then ethanol should be selected in place of methanol as the reactant.

The metal salts used as catalysts in this process along with the acids are generallyy those from group IB, VI, VII and VIII of the periodic table and include in particular such metals as cobalt, iron, copper, nickel, manganese and chromium. Of these, it has been found that iron and copper salts are particularly effective in enhancing the reaction rate of this process. While the nature of the anion of the salt is not particularly critical, it has been found that such anions as sulfate, nitrate, oxalate and chloride may be employed satisfactorily. The yamount of metal catalyst used should be in the 'range of fromabout 0.1 to 5.0 gms. per 50 to 75 gms.

of alcohol-acid solution, and preferably from about vl .0

to 3.0 gms.

The hydroperoxides used in this process include both aliphatic and-alicyclic compounds having from about 3 to l2 carbon atoms for example, alkyl hydroperoxides and methyl substituted cycloalkyl hydroperoxides. The

vhydroperoxides may be either secondary or tertiary compounds, although the latter type are more reactive and thus more effectively employed thanr are the secondary compounds. Typical amongst the aliphatic hydroperoxides are such compounds as t-butyl hydroperoxide or sec.-butylhydroperoxide, while the alicyclicA hydroperoxides include such compounds as lf-me'thylcyclopentyland l-methylcyclohexylhydroperoxide and the like.- It should be understood that while ithe starting materials for this'process desirably hydroperoxide, these peroxides may, in

fact, optionally contain admixed therewith small `amounts of alcohols corresponding to the hydroperoxide, which alcohols are usually formedlduring the oxidation of the corresponding hydrocarbonsr to the respective hydroperoxide. These alcohols generally remain unchanged throughout theinstant process.

When these and similar hydroperoxides are treated in accordance with this process, there are obtained the corresponding aliphatic and alicyclic ethers such as alkyl t-butyl ether, alkyl see-butyl ether, l-methylcyclopentyl alkyl ether and the like.

The temperature employed in effecting this reaction yshould desirably beffrom about 20 to 80C, and preferably from 50 to 60C. Although the reactions can be carried out at atmospheric pressure to give high yields of the desired ethers, it has been found that the yields Carbostyril derivative or a pharmaceutically acceptable (R6)m acid addition salt thereof, having excellent platelate aggregation inhibitory effect, calcium antagonism, hypotensive effect and phosphodiesterase inhibitory effect are useful as prophylactic or treating agents for throm- R7 8 PT- bosis, circulation improving agents for coronary blood l 5 OA(CON'B)0C C-OR flow such as coronary vasodilators, hypotensive agents and phosphodiesterase inhibitors. Furthermore, the 0 I I O carbostyril derivatives are weak in heart rate increasing R3 N R4 activity and also in cardiac muscle contraction increas- H ing activity, and the carbostyril derivatives are useful Carbostyril derivative or a pharmaceutically acceptable 0 acid addition salt thereof, having excellent platelate RS X aggregation inhibitory effect, calcium antagonism, hy- (12) potensive effect and phosphodiesterase inhibitory effect PT are useful as prophylactic or treating agents for throm- (1c) bosis, circulation improving agents for coronary blood flow such as coronary vasodilators, hypotensive agents and phosphodiesterase inhibitors. Furthermore, the carbostyril derivatives are weak in heart rate increasing activity and also in cardiac muscle contraction increasing activity, and the carbostyril derivatives are useful han@ Kr (I 2L 2dr K (l r2)e 2a d carbastyni derivative ar a piramaeeaaeaiiy aecepnble vw aeicl addition salt thereof, having excellent platelate aggregation inhibitory effect. calcium antagonism, liyA potensive ell'ect and phosphodicstemse inhibitory effect 4 PT areuseful as prophylactic or treating agents for throm- 1 bosis, circulation improving agents [or coronary blood l" llow such as coronary vasodilators, hypotensive agents L and phaspnaaiesrerase inhibitors. Furthermore, the carbostyril derivatives are wak in heart rare increasing l, Q activity and also in cardiac muscle contraction inereasr i Q m ing activity, and the carbosiynl derivatives are useful m o 2 I 3 -1 C, O O O -r I o m u m l 8 E 'E E e x if e t a w l K1x+Kv+K3z+n+n K'ix+K a e a a rzequ= K' 7"-0 "o OH-Euuu'w'nmuag--i w+ 32+ aa 5ea`;8a Oo' GE o Q- --w Hm e' -o' 11i-...m n. q'a4-D 0:1 L ^o JHHMI'IL s-i ou g-a-e air v aga 0 www@ s ...e apanage w=v-ss.a8 1 t E -.==Uo'= E--5&,= @ahead-gr 2 22T 2mm om w-= von: gmefe 3 |11 grgimdgg -'u 4 ooo?- UUH: mi* URZEO"" ;,TEJ=" 5 "Fl-X 6 XXX. E awoa @ea-@weine .Ew--on O-=%.2-E'e sew-gamona nmfi O L1 u u u .e u c n o pagos 2no ve120 eeis oO 0 D vecaagw aesa-E 1 Oef-O01 aaoa envar-saai? 111mm 2 ^-O+|+ se -Z s ee a 12@ mmmmmm s if 1""I' a. H.- V1I-V122 E-'g l'll| v Nat-om'- SeO-egiggfigggg l'lllllmmuinm g eaoooco ..QO'U-cwcngo :i n? -gegagl (3i-emma@ 6 a vafa2.i om: g'fesaa'gaaa i771 "JIAIE 'eoannn ooo :QC i 5hnOuOOx=iun HF." 50D 5UomnEnGoonm I m m C g E a 2 U .5 'c b '5 b i 9 a O I 0 N i3 .n 1:1 o s .E o e,

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The product was worked up as described in Example l and the yields of methyl t-butyl ether and dimethoxymethane (based of t-butyl hydroperoxide charged) were 80 and 70 weight percent respectively.

EXAMPLE 13 The procedure of Example l2 was applied to a charge consisting of 0.05 moles of t-butyl alcohol (7.4 grams) and 0.05 mole of t-butyl hydroperoxide. The reaction conditions and quantities of acid, methanol and iron salt remained the same.

Analysis of the product showed it to contain 0.085 moles of methyl t-butyl ether and 0.04 moles of dimethoxymethane.

EXAMPLE l4 in the presence of an acid and metal salt or copper oxide catalyst at a temperature of from about `'to 80C wherein the acid concentration is from about 5 to 30 weight percent based` on the .weight of the acidalkanol mixture, and wherein said metal salt is present i fate. The solution was stirred for 4 hours at 60C under in amounts of from about 0.1 to 5.0 grams per 50 to 75.0 grams of said acid-alkanol mixture, said acid being selected from the group consisting of hydrochloric acid, phosphoric acid, polyphosphoric acid, oleum, sulfuric acid, perchloric acid, a sulfonic acid-type cation exchange resin, and an acid treated molecular sieve, said metal of the metal salt being selected from Groups IB, Vl, Vll and Vlll of the Periodic'Table, and the anion of said metal salt being selected from sulfate, nitrate, and oxalate anions, and recovering the resulting ether and the dialkoxyalkane from the reaction mixture.

2. The process according to claim l wherein the metal salt is a ferrous, ferric or copper salt.

3. The process according to claim l wherein the reaction is carried out under autogenous pressure.

4. The process according to claim l wherein the hydroperoxide is t-butylhydroperoxide, the alkanol is methanol, the metal salt is ferrous or ferric sulfate and the product is a mixture of metyl t-butyl ether and dimethoxymethane.

5. The process according to claim l wherein the acid concentration is from about l5 to 2O weight percent based on the weight of the acid alkanol mixture.

6. The process according to claim l wherein the alkanol is methanol. v

7. The process according to claim l wherein the alkanol is present in a molar excess of at least twice the number of moles of the hydroperoxide starting material.

8. The process according to claim l wherein the metal salt is a cobalt, nickel, manganese or chromium salt.

* it Ik ik 

2. The process according to claim 1 wherein the metal salt is a ferrous, ferric or copper salt.
 3. The process according to claim 1 wherein the reaction is carried out under autogenous pressure.
 4. The process according to claim 1 wherein the hydroperoxide is t-butylhydroperoxide, the alkanol is methanol, the metal salt is ferrous or ferric sulfate and the product is a mixture of metyl t-butyl ether and dimethoxymethane.
 5. The process according to claim 1 wherein the acid concentration is from about 15 to 20 weight percent based on the weight of the acid alkanol mixture.
 6. The process according to claim 1 wherein the alkanol is methanol.
 7. The process according to claim 1 wherein the alkanol is present in a molar excess of at least twice the number of moles of the hydroperoxide starting material.
 8. The process according to claim 1 wherein the metal salt is a cobalt, nickel, manganese or chromium salt. 